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多巴反应性肌张力障碍一家系临床异质性和基因外显率研究

Phenotypic heterogeneity and gene penetrance of a dopa-responsive dystonia family
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摘要 目的探讨多巴反应性肌张力障碍(DRD)一家系的临床异质性和基因外显率情况。方法回顾性分析中日友好医院神经科2015年11月收治的DRD一家系共4代人(3例患者)的临床资料,对先证者进行全外显子基因测序,并采用Sanger测序进行验证,对家系中另外14人进行Sanger测序,分析该家系成员的基因型和临床表现。结果15名进行基因检测的成员中有7人存在GCH1基因c.284G>A(p.P95L)杂合突变,3例有临床症状,该家系基因外显率为0.43(3/7),男性外显率为0.25(1/4),女性外显率为0.67(2/3)。2例女性患者的临床症状均重于男性患者,且2例女性患者临床症状严重程度差异大。结论携带相同基因突变的DRD家系成员临床症状严重程度差异很大,具有明显性别差异,其中男性患者的基因外显率低,临床症状轻微。 Objective To investigate the phenotypic heterogeneity and gene penetrance of a dopa-responsive dystonia(DRD)family.Methods The clinical data of a four-generation DRD family(including 3 patients)admitted to Department of Neurology,China-Japan Friendship Hospital in November 2015 were retrospectively analyzed.The proband underwent whole exon sequence,and the genetic result was verified by Sanger sequencing.Sanger sequencing was performed in the other 14 subjects in the family;the genotypes and clinical manifestations were analyzed.Results In 15 subjects underwent genetic testing,7 had heterozygous mutations c.284G>A(p.P95L)in GCH1 gene;the penetrance of GCH1 gene mutation in this family was 0.43(3/7),the gene penetrance in male was 0.25(1/4),and the gene penetrance in female was 0.67(2/3).Three subjects in the DRD family had clinical symptoms;the clinical symptoms of the two female patients were more severe than those of the male patient;the severity of clinical symptoms differed greatly between the 2 female patients.Conclusion There is a wide intrafamilial phenotypic heterogeneity in DRD family members carrying the same gene mutation,and the phenotype is gender-related;the gene penetrance in male is lower than that in female,and the clinical phenotype is often milder.
作者 孙青 汪仁斌 王康 段晓慧 严莉 彭丹涛 Sun Qing;Wang Renbin;Wang Kang;Duan Xiaohui;Yan Li;Peng Dantao(Department of Neurology,China-Japan Friendship Hospital,Beijing 100029,China)
出处 《中华神经医学杂志》 CAS CSCD 北大核心 2022年第11期1153-1157,共5页 Chinese Journal of Neuromedicine
关键词 多巴反应性肌张力障碍 GTP环化水解酶1 基因外显率 Dopa-responsive dystonia GTP cyclohydrolase 1 Gene penetrance
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